Chapter 7: Neurotransmitters & Neuromodulators

The text systematically categorizes chemical mediators into small-molecule transmitters (such as amino acids and monoamines), large-molecule neuropeptides (including substance P and opioids), and gas transmitters (like nitric oxide and carbon monoxide). A core focus is placed on the five sequential steps of neurotransmission: precursor uptake, enzymatic biosynthesis within the nerve terminal, vesicular storage via transporters like VMAT, calcium-dependent release into the synaptic cleft, and signal termination through reuptake transporters (such as NET and SERT) or enzymatic degradation. The chapter distinguishes between fast synaptic transmission mediated by ionotropic receptors (ligand-gated ion channels) and slower neuromodulation involving metabotropic G-protein-coupled receptors (GPCRs), which utilize second messengers like cAMP, IP3, and DAG. Detailed physiological profiles are provided for major excitatory transmitters like glutamate, discussing its role in excitotoxicity and its action on AMPA, Kainate, and NMDA receptors, the latter of which requires glycine binding and membrane depolarization to relieve magnesium blockage. Conversely, the chapter explores inhibitory transmission via GABA and glycine, which hyperpolarize neurons by increasing chloride conductance, a process modulated by benzodiazepines. The discussion extends to the monoamines—dopamine, norepinephrine, epinephrine, and serotonin—tracing their synthesis from tyrosine and tryptophan, their receptor subtypes (such as alpha-adrenergic and beta-adrenergic receptors), and their clinical relevance in psychiatric disorders treated with SSRIs and MAO inhibitors. Additionally, the summary covers the cholinergic system's reliance on acetylcholinesterase, the analgesic properties of opioid peptides acting on mu, kappa, and delta receptors, and the unique retrograde signaling mechanisms of endocannabinoids and diffusible gas transmitters that activate guanylyl cyclase.